Influence of enhancer sequences on thymotropism and leukemogenicity of mink cell focus-forming viruses
Authors
Holland, Christie A.Thomas, Christopher Y.
Chattopadhyay, Sisir K.
Koehne, Charles F.
O'Donnell, Paul V.
UMass Chan Affiliations
Department of Radiation OncologyDocument Type
Journal ArticlePublication Date
1989-03-01Keywords
Amino Acid SequenceBase Sequence
Cloning, Molecular
*Enhancer Elements (Genetics)
Genetic Engineering
Leukemia Virus, Murine
Leukemia, Experimental
Mink Cell Focus-Inducing Viruses
Molecular Sequence Data
Nucleotide Mapping
Regulatory Sequences, Nucleic Acid
Retroviridae Proteins
Thymus Gland
Viral Envelope Proteins
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Oncogenic mink cell focus-forming (MCF) viruses, such as MCF 247, show a positive correlation between the ability to replicate efficiently in the thymus and a leukemogenic phenotype. Other MCF viruses, such as MCF 30-2, replicate to high titers in thymocytes and do not accelerate the onset of leukemia. We used these two MCF viruses with different biological phenotypes to distinguish the effect of specific viral genes and genetic determinants on thymotropism and leukemogenicity. Our goal was to identify the viral sequences that distinguish thymotropic, nonleukemogenic viruses such as MCF 30-2 from thymotropic, leukemogenic viruses such as MCF 247. We cloned MCF 30-2, compared the genetic hallmarks of MCF 30-2 with those of MCF 247, constructed a series of recombinants, and tested the ability of recombinant viruses to replicate in the thymus and to induce leukemia. The results established that (i) MCF 30-2 and MCF 247 differ in the numbers of copies of the enhancer sequences in the long terminal repeats. (ii) The thymotropic phenotype of both viruses is independent of the number of copies of the enhancer sequences. (iii) The oncogenic phenotype of MCF 247 is correlated with the presence in the virus of duplicated enhancer sequences or with the presence of an enhancer with a specific sequence. These results show that the pathogenic phenotypes of MCF viruses are dissociable from the thymotropic phenotype and depend, at least in part, upon the enhancer sequences. On the basis of these results, we suggest that the molecular mechanisms by which the enhancer sequences determine thymotropism are different from those that determine oncogenicity.Source
J Virol. 1989 Mar;63(3):1284-92.Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38732PubMed ID
2536834Related Resources
Link to Article in PubMedCollections
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